1. Field of the Invention
This invention is directed to methods for preparing factor Xa inhibitors and salts thereof.
2. State of the Art
Factor Xa is a serine protease, the activated form of its precursor factor X, and a member of the calcium ion binding, gamma carboxyglutamic acid (GLA)-containing, vitamin K dependent, blood coagulation factors. Factor Xa appears to have a single physiologic substrate, namely prothrombin. Since one molecule of factor Xa may be able to generate greater than 1000 molecules of thrombin (Mann, et al., J. Thrombosis. Haemostasis 1: 1504-1514, 2003), direct inhibition of factor Xa as a way of indirectly inhibiting the formation of thrombin has been considered an efficient anticoagulant strategy.
Several classes of small molecule factor Xa inhibitors have been reported, for example, those described in U.S. Pat. Nos. 7,521,470, 7,696,352, and 7,763,608, U.S. Patent Application Publication Nos. 2007/0066615, 2008/0293704, and 2008/0051578, all of which are incorporated by reference in their entirety.